Description: AD and PD are characterized by distinct clinical and neuropathological abnormalities. However, an AD-like dementia is often found in PD patients, and PD-like extrapyramidal signs are common in AD. Neurofibrillary tangles (NFT) and senile plaques (SP) are hallmark brain lesions of AD, and LBs are neuropathological signatures of PD, but abundant NFTs and SPs also occur in brains of demented PD patients, and AD brains frequently contain many cortical and subcortical LBs. Thus, lesions often overlap between these conditions. The reasons for this are uncertain, but they may reflect similarities in the neurodegenerative mechanisms underlying these disorders. Now, new opportunities to investigate this possibility have emerged from advances in understanding the molecular neuropathology of PD and AD, since the non-amyloid component (NAC) of AD amyloid plaques has been identified and the NAC precursor protein (NACP) is known to be AS. Specifically, it is now known that: 1) mutations in the synuclein gene cause familial PD; 2) wild-type AS forms LB-like filaments and is a major component of LBs in PD, LBVAD and DLB; 3) AS-positive LBs occur in greater than 60 percent of familial AD brains and greater than 50 percent of Down?s syndrome brains with AD; and 4) GCIs in MSA are formed by AS filaments. Moreover, this laboratory has recently detected novel dystrophic processes in the hippocampus of PD and DLB brains with antibodies to g-synuclein. Thus, all three of these synucleins may be implicated in the brain degeneration of PD, AD and related disorders. For these reasons, projects 1-4 attempt to elucidate the role synuclein pathology plays in the onset and progression of AD, PD and related neurodegenerative diseases characterized by synuclein lesions. This core will support the research pursued in these projects by obtaining and characterizing postmortem brains from controls and patients with PD, AD, LBVAD, DLB, MSA or related disorders, and providing samples from these brains to investigators in projects 1-4. Additionally, the core will monitor potential risk-factor alleles for synucleinopathies in study subjects and provide advice as well as technical support to investigators in all four projects using human brain tissues in their research.